CCDC78 (coiled-coil domain containing 78) is a multifunctional protein with distinct roles in muscle physiology and cilia organization. In skeletal muscle, CCDC78 localizes to the sarcoplasmic reticulum (SR) where it interacts with key SR proteins including SERCA1 and CASQ1, as well as sarcomeric proteins MYH1, ACTN2, and ACTA1 1. The protein plays a critical role in organizing the distal tips of motile cilia in multiciliated cells, where it exhibits microtubule-bundling activity and is required for normal cilia length regulation and beating patterns 2. CCDC78 mutations are associated with autosomal dominant centronuclear myopathy-4 (CNM4), characterized by distinctive muscle histopathology including dilated sarcoplasmic reticulum and core-like lesions 1. Genetic variants in CCDC78 can act as disease modifiers, as demonstrated in a family where a CCDC78 variant exacerbated LMNA-related muscular dystrophy, leading to abnormal accumulation of CCDC78 and RyR1 in muscle cores 3. The protein is also recognized as a causative gene for core myopathies 4. These findings establish CCDC78 as an essential component for both muscle SR function and motile cilia organization, with significant implications for understanding neuromuscular diseases and ciliopathies.